HUMAN TUMOR-ASSOCIATED MACROPHAGES DIFFERENTIATE INTO OSTEOCLASTIC BONE-RESORBING CELLS

Macrophages are commonly found within osteolytic secondary carcinomas in bone, but the manner in which these cells contribute to malignant b one resorption is uncertain. Macrophages isolated from primary breast carcinomas mere co-cultured for up to 21 days with UMR 106 rat osteobl ast-like cells on bone slices and glass coverslips in the presence and absence of 1,25-dihydroxyvitamin D-3 \1,25(OH)(2)D-3\ and human macro phage colony stimulating factor (M-CSF). Cell cultures were then asses sed for the presence of phenotypic markers of macrophage and osteoclas t differentiation. Isolated cells were negative for osteoclast markers including tartrate-resistant acid phosphatase (TRAP), vitronectin rec eptor (VNR), and the ability to Carry our lacunar bone resorption, but were positive for CD11b and CD14, macrophage markers which are not pr esent on osteoclasts. In 21-day co-cultures of breast carcinoma tumour -associated macrophages (TAMs) and UMR 106 cells, incubated in the pre sence of 1,25(OH)(2)D-3 and M-CSF, numerous TRAP- and VNR-positive mul tinucleated cells capable of extensive lacunar resorption were formed. Contact with UMR 106 cells and the presence of 1,25(OH)(2)D-3 and M-C SF were absolute requirements for differentiation of human breast carc inoma TAMs into mature functional osteoclasts. TAM-osteoclast differen tiation may represent an important cellular mechanism of osteolysis in metastatic skeletal carcinomas. (C) 1998 John Wiley & Sons, Ltd.